(B) Lecture 14: Tuberculosis and Leprosy Flashcards

1
Q

Mycobacteria

A
  • M. tuberculosis
  • M. leprae
  • M. bovis
  • M. avium
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2
Q

M. tuberculosis is the agent for…

A
  • causative agent of Tuberculosis in humans
  • often called TB for tubercle bacilli
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3
Q

M. leprae is the agent for…

A

causative agent of Leprosy in humans

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4
Q

M. bovis is the agent for…

A
  • causes tuberculosis in cows, rarely in humans
  • humans can be infected by consumption of unpasteurized milk leading to extrapulmonary TB
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5
Q

M. avium

A

can cause TB-like illness in humans, especially in patients w/ AIDS
- usually in immunocompromised patients

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6
Q

Tuberculosis

A
  • infection by M. tuberculosis
  • can be latent (not transmissible) or active (transmissible)
  • approx. 2 billion ppl (1/4 of world’s population) likely have latent TB
  • TB is contagious + spreads through air by ppl w/ ACTIVE TB
  • about 10% of ppl infected w/ latent TB develop active TB in their lifetime
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7
Q

Order of mortality of pathogens

A
  1. COVID
  2. TB
  3. HIV/AIDS
  4. Malaria
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8
Q

Mycobacterium tuberculosis

A
  • INTRACELLULAR pathogen (lives within macrophages)
  • SLOW generation time
  • M. tuberculosis can be grown in the lab on specialized media
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9
Q

M. tuberculosis cell envelope

A
  • have an unusual cell envelope w/ high conc of mycolic acid = WAXY
  • impermeable to stains and dyes (gram POSITIVE ACID FAST STAIN) - hallmark
  • lipid rich/waxy envelope is very hydrophobic and resists common stains
  • mycolic acid causes “acid-fastness”

Unusual cell envelope is associated w/ resistance to:
- some antibiotics
- osmotic lysis via complement deposition
- lethal oxidative stress = survival inside of macrophages

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10
Q

Acid fast stain

A
  1. stained w/ carbol-fuschin dye w/ slow heating to melt wax
  2. washed w/ ethanol and HCl
  3. counter stained w/ methylene blue
  4. acid-fast organisms (like TB) appear red while non-acid fast organisms appear blue
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11
Q

Spread of TB

Stage 1

A
  • transmission thru inhalation of droplets from infected host (coughing/sneezing)
  • small droplets can stay airborne for extended periods of time
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12
Q

Spread and Progression of TB

Stage 2

A
  • lung macrophages phagocytose TB cells
  • TB blocks acidification of phagosome
  • TB inhibits fusion of lysosome to phagosome
  • TB multiplies in macrophages
  • macrophages lyse + release TB cells to infect more macrophages
  • TB delays dendritic cell migration to lymph nodes
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13
Q

ESX secretion systems

A
  • 5 ESX systems exist in M. TB
  • enables transport of select bacterial molecules across thick Mtb cell envelope
  • multiple functions like damage to phagosome membrane
  • also inhibits immune responses
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14
Q

Spread and progression of TB

Stage 3

A
  • infected macrophages form GRANULOMAS
  • TB granulomas are TUBERCLES of immune cells that try to destroy invading pathogens

granuloma represents a balance btwn pathogen and host = LATETNT INFECTION

  • T-cell activated macrophage can kill TB
  • activated T cells secrete cytokines (IFN-gamma) to activate macrophage
  • macrophages at centre of granuloma are harder to activate by T cells
  • chronic inflammation causes cheese-like necrosis = CASEOUS NECROSIS
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15
Q

Spread and progression of TB

Stage 4

A
  • some macrophages remain unactivated and infected
  • tubercle grows
  • granuloma erodes into airway = route of transmission
  • deterioration of host immunity = active TB
  • caseous centre/lesions can liquefy and cause CAVITATION
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16
Q

Extrapulmonary TB

A
  • infection OUTSIDE the lungs
  • can infect multiple organ systems
  • more likely to occur in immunocompromised

MILIARY TB (tiny lesions) = widespread dissemination (almost always fatal)

17
Q

Testing and Diagnosis of TB

A
  • Tuberculin test is injected under skin
  • T cell-mediated response (2 days after)
  • positive result= red and swollen at 48h
  • infected if they convert from negative to positive on TB skin test
  • a positive tuberculin test would mean a careful history and a chest X-ray
  • X-ray: typical upper lobe shadow = lesions
  • calcified granulomas may be seen on X-ray
  • staining of sputum for acid fast
  • IFN-gamma response assay (look at T cell specific response)
18
Q

TB Test results

A

Positive test = red and swollen at 48h

Positive result could mean
- latent or active TB, BCG vaccinated, previously infected

Negative test could mean
- not infected, immune compromised, not infected long enough

19
Q

Treatment of TB

A
  • active TB can kill 2 of 3 ppl if untreated
  • 6 months of antibiotics for short treatment
  • slow growth = long treatments

Multiple types of antibiotics used
- Rifampin
- Isoniazid

20
Q

Drug Resistant TB

A

Multi-drug resistant TB (MDR-TB)
- being resistant to the two most effective first-line therapeutic drugs, isoniazid and rifampin

Extensively-drug resistant (XDR-TB)
- resistant to the most effective second-line therapeutic drugs used to treat MDR-TB

BUT new drugs are being developed.

21
Q

Rifampin

A

antibiotic used to treat TB
- first-line drug

inhibits RNA Polymerase

22
Q

Isoniazid

A

antibiotic used to treat TB
- first-line drug

inhibits mycolic acid synthesis)

23
Q

BCG

A

bacille Calmette-Guerin

  • LIVING vaccine prepared from attenuated M. bovis
  • no ESX-1 secretion system (less virulent)
  • controversial due to variable efficacy for pulmonary TB
  • effective agianst miliary TB
  • vaccinated ppl can give a false positive for tuberculin test

recommended for ppl w/ high risk to exposure

24
Q

Leprosy

A
  • chronic disease caused by M. leprae
  • also called Hansen’s disease
  • very SLOW progression (incubation of about 5 years)
  • can cause permanent damage to skin, nerves, limbs, eyes
  • rare in high income countries
  • mainly in tropical, developing countries
  • victims have been ostracized
  • lesions are visible
25
Q

M. leprae

A

gram-POSITIVE acid fast, rod shaped, waxy cell envelope (mycolic acid)

  • cannot be cultivated in vitro/labs
  • infects macrophages of skin + Schwann cells in nerves
  • can grow in foot pads of mice
  • causes systemic infection in armadillo
26
Q

Leprosy vs TB

A
  • TB lesions are hidden while leprosy lesions are visible
  • leprosy is much LESS infectious than TB
27
Q

Major forms of Leprosy

A

Tuberculoid and Lepromatous

28
Q

Tuberculoid Leprosy

A
  • cell-mediated immunity present
  • macrophage can contain bacteria
  • light coloured lesions w/ anesthetic areas
  • become tuberculin positive (active T cell-mediated responses)

Tuberculoid Leprosy can be self-limiting (immune system wins + kills pathogens)

29
Q

Lepromatous Leprosy

A
  • cell-mediated responses are ABSENT
  • macrophages are NOT activated
  • M. leprae survives and multiplies in macrophages + Schwann cells
  • nerve damage + loss of sensation = inadvertent traumatic lesions on face + extremities
  • can cause loss of eyebrows, thickening and enlarged ears and cheeks = LION-like appearance
  • lesions can be secondarily infected = bone resorption, disfigurements and mutilation
30
Q

Leprosy damage to nerve cells

A

damage to nerve cells is INDIRECT
- caused by MACROPHAGES

31
Q

Spread and progression of Leprosy

A
  • transmission is not well understood
  • likely need direct contact for extended periods of time - inhaled droplets?
  • most exposed individuals do not develop disease (host genetics are important)
32
Q

Leprosy and antibiotics

A

Leprosy is treatable w/ antibiotics
- multidrug therapy (MDT) with 3 antibiotics
- 6 months to 1 year
- patients are thought to no longer transmit the diseases after one dose of MDT
- ultimate goal is elimination of leprosy